Surgical Oncology Board Review - Breast Cancer

There is debate regarding optimal management, with both follow up imaging and surgical excision as reasonable options. Note that aggressive features of LCIS include: pleomorphic LCIS, any associated necrosis. Usual type LCIS (<4 terminal ductal lobular units in a single core) can likely be safely followed every 6-12 months provided there is no clinical or radiographic discordance.

Consider tamoxifen for risk reduction.

- Lumpectomy + radiation (preferred as radiation halves risk of local recurrence)
- Total mastectomy

- Lumpectomy alone (if deemed "low" risk)

- If ER positive and pt opts for lumpectomy/XRT, add tamoxifen to reduce ipsilateral breast cancer

- H&P and imaging q6-12 months x 5 years

- For patients undergoing lumpectomy/XRT, first mammogram should be done 6 months after completion of radiation

At least 25%

Absolute:

- Pregnant women who would require RT during pregnancy

- Diffuse suspicious microcalcifications

- Widespread disease that cannot be incorporated by local excision with a single incision with satisfactory cosmetic result

- Positive pathologic margins (consider re-excision followed by mastectomy if still positive)

Relative:

- Prior radiation to breast/chest wall (check dose)

- Active connect tissue disease, ie scleroderma and lupus

- Tumors > 5cm

- Focally positive pathologic margins (consider re-excision vs higher radiation boost)

"The 25-year findings from that study showed that there was no significant difference in survival between women treated with the Halsted radical mastectomy and those treated with less extensive surgery." -Fisher 2002

RCT to see whether lumpectomy with or without radiation therapy was as effective as total mastectomy for the treatment of invasive breast cancer --> No OS difference

Milan trial - lumpectomy + ax dissection vs Halsted mastectomy for early cancer --> breast conservation was equivalent

Metastatic workup is indicated for clinical Stage IIIA and above disease (T3 N1)

Obtain bone scan OR PET scan, CT OR MRI abdomen/pelvis, and CT chest

Positive axillary nodes, lymphovascular invasion, young age, high grade disease

Positive lymph nodes (Definitely 4+, strongly consider for 1-3)

Consider internal mammary node bed radiation to all patients with positive nodes (NCIC-CTG MA20 - RCT showed lower LR and trend towards lower OS)

Women >/= 70 years old with clinically negative lymph nodes and ER-positive, T1 breast cancer

Must prescribe hormonal therapy for these patients!

In patients with H&E negative SLN, further examination by IHC was not associated with improved OS

Thus H&E alone is sufficient, but if equivocal should perform IHC

RCT which compared SLN biopsy alone vs ALN dissection in women with T1/T2 tumors, 1 or 2 positive SLNs, and undergoing lumpectomy with radiation --> No difference in LR, DFS, or OS between groups

Thus completion axillary dissection may be omitted in these patients

ALN should include level I and level II nodes. All tissue inferior to the axillary vein from the latissimus dorsi muscle laterally to the medial border of the pectoralis minor muscle should be removed.

Level III nodes should be removed only if there is gross disease in Level II.

Breast conservation rates are higher after neoadjuvant chemotherapy

There is no demonstrated survival advantage over adjuvant therapy

Node-positive disease (Definitely for 4+, strongly considered for 1-3)

Tumor size > 5cm

Close (<1mm) or positive margins

Luminal A/B: ER+, HER2-

Basal subtype: ER-, HER2- (triple negative)

HER-2 positive

ER/PR+, HER2-: T1b or higher (>0.5cm), N0

Use the score to estimate likelihood of recurrence and benefit of chemotherapy

Don't send Oncotype on triple negative or HER2 positive tumors. Most should get chemo. However areas of uncertainty include:

HER2+: T1a, N1mi or T1b, N0

ER/PR-, HER2-: T1a, N1mi or T1b, N0

In these patients consider other risk factors. For example patients above 70 may not benefit.

Paclitaxel, cyclophosphamide: TC x 4 cycles (12 weeks total)

Trastuzumab for any HER2 positive patients with tumors >1cm (AC x 4 cycles (12 weeks)--> TH weekly (12 weeks) or TCH given cardiotoxicity risk with trastuzumab and doxorubicin), and consider pertuzumab

Following lumpectomy:

Mastectomy with level I/II dissection

Consider repeat SLN biopsy

Following mastectomy:

Local excision if negative margins achievable

Surgery after initial systemic therapy should be considered for women requiring palliation or with impending complications such as skin ulceration, bleeding, fungation, and pain

Radiation can be considered as alternative

Removal of NAC and underlying tumor if present, can do total mastectomy or central lumpectomy with SLN biopsy

If no associated tumor/mass, perform central lumpectomy (no need for SLN biopsy)

Wide local excision with 1 cm margin

No SLN biopsy

No adjuvant chemotherapy

Adjuvant radiation (50-60 Gy) for malignant tumors > 5cm

At least 2mm

If less <1mm at borders such as skin or chest wall consider boost of radiation instead of re-excision

**There are no studies to date that demonstrate improved survival with addition of MRI.

- Define extent of cancer in the presence of multifocal or multicentric cancer in the ipsilateral breast

- Screen contralateral breast in high risk patients

- Before/after neoadjuvant therapy to determine disease extent, response, and potential for breast conservation

- Dense breast

- Identify occult primary in patients with axillary nodal adenoCA or Paget's with no primary identified on mammo/US/exam

- False positives are common so must get core biopsy of suspicious areas seen only on MR

- F/u surveillance in women with second primary breast cancer risk > 20%

Tis - DCIS/LCIS

T1mi - <0.1cm

T1a - 0.1-0.5cm

T1b - 0.5cm - 1cm

T1c - 1cm-2cm

T2 - 2cm-5cm

T3 - >5cm without direct chest wall extension

T4 - Tumor of ANY size with direct chest wall or skin invasion

-- T4a - Extension to chest wall

-- T4b - Ulceration or satellite nodules or peau d'orange of the skin

-- T4c - BOTH T4a + T4b

-- T4d - Inflammatory carcinoma

N0 - no positive nodes

N1 - Movable ipsilateral level I or II axillary nodes

N2a - Mets in ipsilateral level I or II axillary nodes fixed or matted

N2b - Mets in only clinically detected ipsilateral internal mammary nodes in the absence of other nodal mets

N3a - Ipsilateral infraclav node

N3b - Ipsilateral internal mammary node AND axillary node

N3c - Ipsilateral supraclavicular lymph node

Stage IA - T1 N0 M0

Stage IB - T0 N1mi M0; T1 N1mi M0

Stage IIA - T0 N1 M0, T1 N1 M0

Stage IIB - T2 N1 M0, T3 N0 M0

Stage IIIA - T0 N2 M0, T1 N2 M0, T2 N2 M0, T3 N1 M0, T3 N2 M0

Stage IIIB - T4 N0 M0, T4 N1 M0, T4 N2 M0

Stage IIIC - Any T N3 M0

Stage IV - Any T Any N M1

IBC is a clinical diagnosis based on erythema AND peau d'orange of a third or more of the skin of the breast with a palpable border to the erythema. Typically ER/PR - and often HER2 +.

Full staging workup. Neoadjuvant chemotherapy. Modified radical mastectomy. Adjuvant radiation and additional chemotherapy (chemotherapy sandwich approach).

Any individual with breast cancer diagnosis AND:

- Known mutation in cancer susceptibility gene within the family

- Early age onset breast cancer (< 50 years)

- Triple negative breast cancer < 60 years

- 2 breast cancer primaries

- Family history: 1 or more close blood relative with BC < 50, 1 or more close blood relative with ovarian cancer at any age, 3 or more close blood relatives with BC or panc cancer at any age, population at increased risk

About 10% of breast cancer is linked to mutations in single genes

BRCA1/2

Li-Fraumeni (p53)

Cowden (PTEN)

Hereditary diffuse gastric cancer (CDH1) - lobular breast ca

Repeat core biopsy

If no imaging finding remains, consider wire localized excisional biopsy for definitive diagnosis

Lesions often recur but they are not associated with cancer risk. Can observe and perform surveillance

Consider excision if strong family history of breast CA or any suspicious clinical features

Case report of tamoxifen to limit growth (NOT for cancer risk). Lesion will usually increase in size again when tamoxifen is stopped.

Common in young, Asian women within 5 years post pregnancy.

Do NOT excise as may get persistent wound healing problems.

Reassure. Usually self-limited.

Usually due to intraductal papilloma but need to exclude malignancy

- Mammogram & ultrasound to evaluate for underlying mass

- Ductogram to identify intraductal lesion if present. Can only be done if discharge can be reproduced on exam and the affected duct can be cannulated

- (Ductoscopy, rarely used in US)

- Central duct excision

When atypical ductal hyperplasia is found on core needle biopsy, subsequent excisional biopsy will demonstrate invasive cancer 15% of the time (compare to about 25% upstaging of DCIS). Therefore excision is recommended as well as tamoxifen. NSABP P-1 showed that tamoxifen reduces risk of developing breast cancer in half in women with atypia without breast cancer on final pathology.

PTEN mutation

Breast cancer (up to 50%)

Endometrial cancer

Follicular thyroid cancer

Think of milking (breast) 10 (pTEN) female (endometrial) cows (Cowden) in a FOLiage (follicular thyroid) green field

STK11 mutation

Breast cancer (up to 50%)

Ovarian cancer

Uterine cancer

Hamartomatous GI polyps

Melanin deposits in mouth/lips/fingers/toes

11 (STK11) women praying from the pews with GI hamartomatous Polyps, Even more melanin deposits, and Unfortunate triad of breast, ovarian, and uterine cancers

P53 mutation

**Frequently have radiation induced tumors so mastectomy preferred

**Strikingly high rates of cancer

Adrenal corticocarcinomas

Breast cancer

Brain cancer

Leukemias

Sarcomas & osteosarcomas

Leukemias

In your head (Brain) cancers

Filled with sarcoma & osteosarcoma

Radiation induced tumors (so do mastectomy)

Adrenal corticocarcinoma

Unforunate breast cancer

Mutation in p53

Evil

Number of

Icky cancers

• Tumor >5 cm

• Direct extension to chest wall or skin-ulceration, edema, skin nodules in ipsilateral breast

• Inflammatory breast cancer

• Fixed or matted axillary nodes

• Supraclavicular nodes

• Internal mammary nodes

• Infraclavicular nodes

Small cells which infiltrate mammary stroma and adipose tissue in a single file pattern due to absence of E-cadherin.

Lobular carcinoma is usually ER/PR+, HER2-, but HER2+ subtypes do exist.

Lobular cancers respond less well to neoadjuvant chemotherapy than ductal carcinomas.

Prognosis is similar

- large tumor size

- close proximity to NAC / centrally located

- multifocal or multicentric disease

- poorly differentiated

- lymphovascular invasion

- extensive intraductal component

- stage of tumor

- positive nodes

Relative

- BRCA mutation carrier or family history

- presence of ptosis

- history of prior surgery at or around the NAC.

~ 90%

40% lifetime risk

Score < 18 --> little benefit of adjuvant chemotherapy

Score 18-30 --> intermediate benefit of adjuvant chemotherapy

Score > 30 --> likely benefit of adjuvant chemotherapy

Completion mastectomy (since you cannot give more radiation)

Repeat sentinel lymph node biopsy if it was done the first time, no axillary surgery if axillary dissection completed previously

Hormone therapy

Benefit of systemic chemotherapy for ipsilateral recurrence not well demonstrated, can decide based on nodal disease

pN0(i+) = tumor deposit ≤ 0.2 mm

pN1mi = tumor deposit > 0.2 mm but ≤ 2 mm

Stage IA - T1 N0 M0

Stage IB - T0 N1mi M0 or T1 N1mi M0

Stage IIA - T0 N1 M0, T1 N1 M0

Stage IIB - T2 N1 M0, T3 N0 M0

Stage IIIA - T0 N2 M0, T1 N2 M0, T2 N2 M0, T3 N1 M0, T3 N2 M0

Stage IIIB - T4 N0 M0, T4 N1 M0, T4 N2 M0

Stage IIIC - Any T N3 M0

NSABP-32

ALMANAC

Streptococcus pyogenes

Even amount of stromal and epithelial cells, uniform stroma

Rarely helpful

Lots of false positives and negatives

Can't tell fibroadenoma vs phyllodes on FNA alone, so get core

Ducts completely filled and exhibit sharp punched out spaces or micropapillae

- Lack uniform cytologic features

- Columnar cells or focal streaming of cells

OR

Ducts filled by a uniform population of cells with cytologic features of low grade DCIS but lack architectural features

- Partial filling of ducts

- Lack of uniformly sharp punched out spaces, microacini or characteristic micropapillae

(Solid low grade DCIS is rare but must be excluded before using this feature to diagnose ADH)

OR

Cytologic and architectural features met but failure to meet size criteria

- Fewer than two duct spaces involved or less than 2-3 mm in aggregate dimension

All get wide local excision with 1cm
NO axillary staging

Malignant tumors >5cm --> adjuvant RT

Staph aureus (including MRSA)

Yes

No, but should be considered in refractory cases

~3% (USPSTF)

No. Reserve metastatic workup for IIIA disease: T3 N1 M0 (>5cm) or Any T N2 disease, regardless of hormonal status.

Breast MRI Screening recommended:

- BRCA carrier, Li Fraumeni, Cowden

- First degree relative of BRCA carrier, untested

- Lifetime risk > 20% based on risk model

- Hx of radiation to chest wall in childhood

(ACS guidelines)